This invention was made in the course of work supported by the United States Government, which has certain rights in the invention.
The field of the invention is probes for radiance dosimetry.
The spatial distribution of radiance in tissue is of fundamental importance in many applications of photobiology and laser medicine. For example, in photodynamic therapy of solid tumors, irradiation of the tissue with energy of appropriate wavelength following administration of a photosensitizing dye leads to tumor destruction. The efficacy and safety of this treatment depends, among other factors, on delivering an adequate radiant energy fluence (J/cm.sup.2) throughout the target tumor tissue, while sparing as far as possible the adjacent normal tissue.
There are two general approaches to determining radiant energy fluence distributions in tissue: (1) to measure the optical absorption and scattering properties of the tissue at the wavelength of interest and then to use these data to calculate the spatial distribution of fluence or absorbed energy using an approximate analytic or numerical model of light transport such as diffusion theory (Doiron et al., in Porphyrin Photosensitization; Kessel et al., eds. pp. 63-76, Plenun, N.Y., 1983; Ishimau et al., Appl. Opt. 28:2210, 1989; Flock et al., IEEE Trans. Biomed. Eng., 1986) or Monte Carlo simulation (Flock et al., supra; Jaques et al., Appl. Opt. 28:2223, 1989); and (2) to measure directly the fluence rate at the point of interest within the tissue during irradiation. The first, indirect method has the advantage that it may be possible to determine the average tissue optical properties, and hence the fluence distribution, at all points non-invasively, for example by diffuse reflectance spectroscopy. The accuracy of this method is likely to be limited in the case of small tissue volumes of complex shape or if the tissue is optically heterogeneous on a scale comparable to the distances over which changes in radiance fluence are significant (Yoon et al. Applied Optics 28:2250, 1989).
The second, direct method is necessarily invasive and only a limited number of localized measurements can be made. In addition, a major challenge has been to make interstitial probes which have an isotropic response. For example, using a cut-end optical fiber connected to a photodetector, only radiance within a restricted solid angle determined by the numerical aperture is collected. The signal measured at a given orientation then depends on the radiance pattern at the specific location in the tissue. Hence, unless the radiance field is isotropic at this location, it is necessary to integrate the measurements from several directions. This has been done in vivo (Doiron et al., supra; Wilson et al., Photochem. Photobiol. 47:153, 1975) and has the advantage that very small diameter fibers may be used which can be placed in tissue easily and relatively non-traumatically, but this may not be a generally applicable technique. In order to measure the true fluence by a single measurement even in an anisotropic field, optical fiber probes have been developed with a spherical tip which is highly light scattering (Star et al., Photochem. Photobiol. 46:619, 1987; Marijnissen et al., Laser Med. Surg. 7:235, 1987; Star et al., Appl. Opt. 28:2281, 1989; Marijnissen et al., in Photodynamic Therapy of Tumors and of Diseases, Jori et al., eds., pp. 387-380, Libreria Progetto, Padua, 1985). Such probes have an approximately isotropic response, between the forward direction and about 150.degree., the backward direction having low response because of shielding where the fibers are attached to the tip. Within this angular range, isotropy of about .+-.10% has been achieved with 800 .mu.m diameter tips on a 400 .mu.m core fiber. The scattering tip of this type of probe must be large enough to make the response isotropic. Further, scattering ball tips are often quite fragile, and this characteristic makes it difficult to use them safely and easily in many solid tissues. They have been widely used for studies in liquids or gel tissue-simulating phantoms and for monitoring within body cavities such as the bladder (Star et al., Photochem. Photobiol. 46:619, 1987; Marijnissen et al., in Photodynamic Therapy of Tumors and of Diseases, Jori et al., eds., Libreria Progetto, Padua, 1985).